MOLECULAR CHARACTERIZATION OF A FAMILY OF LIGANDS FOR EPH-RELATED TYROSINE KINASE RECEPTORS

A family of tyrosine kinase receptors related to the product of the ep h gene has been described recently. One of these receptors, elk, has b een shown to be expressed only in brain and testes. Using a direct exp ression cloning technique, a ligand for the elk receptor has been isol ated by screening a human placenta cDNA library with a fusion protein containing the extracellular domain of the receptor. This isolated cDN A encodes a transmembrane protein. While the sequence of the ligand cD NA is unique, it is related to a previously described sequence known a s B61. Northern blot analysis of human tissue mRNA showed that the elk ligand's mRNA is 3.5 kb long and is found in placenta, heart, lung, l iver, skeletal muscle, kidney and pancreas. Southern blot analysis sho wed that the gene is highly conserved in a wide variety of species. Bo th elk ligand and B61 mRNAs are inducible by tumour necrosis factor in human umbilical vein endothelial cells. In addition, both proteins sh ow promiscuity in binding to the elk and the related hek receptors. Si nce these two ligand sequences are similar, and since elk and hek are members of a larger family of eph-related receptor molecules, we refer to these ligands as LERKs (ligands for eph-related kinases).